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9/05/2012 SD, male 40 yrs. old. (680718M467.) -2002: Rectal blood loss, UC? (no definite diagnosis) rectal mesalazine -June 2008: Recurrence of rectal blood loss and urgency Total colonoscopy: ulcerative rectitis, Mayo 2, otherwise normal Biopsies suggestive of ulcerative colitis Treated with oral mesalazine, no response Rectal mesalazine added (4 g enema) -Oct 2008: Hospital admission Abdominal pain, diarrhea (10x/d, 2x/night), fever (38°C), rectal blood loss Sigmoidoscopy: active rectitis, up from 10 cm normal vascular pattern, islands of mucopus, pseudomembranes Stool enteropathogens on day of admission -C diff toxine A/B negative, parasites negative -other pathogens: no reply yet Colonoscopy 1 9/05/2012 B-1495372 Biopsy What is your diagnosis? • Normal biopsy • Non-specific colitis • Infectious colitis • Ulcerative colitis 2 9/05/2012 Pseudomembranous colitis Clostridium difficile colitis Type I Type II 3 9/05/2012 Clostridium difficile colitis – Antibiotic associated colitis Microscopic patterns • • • • Normal Oedema Active – infectious type colitis Pseudomembranous colitis (97% C diff +) • Type I summit lesion • Type II Focal crypt lesion • Type III confluent mucosal necrosis – Fulminant type 4 9/05/2012 Pseudomembranous colitis DD Ischemia Borriello e.a. JJ Med Microbiol 1987; 24: 53 • Antibiotic-associated diarrhea – Diarrhea related to a recent course of antibiotics but with no microscopic evidence of mucosal disease – C. difficile positive in 6% of patients • Antibiotic-associated colitis – Diarrhea with histological evidence of colitis that is not pseudomembranous – C. difficile positive in 38% of cases 5 9/05/2012 Present biopsy - Mild architectural abnormalities - No hyalinization -Limited active inflammation (duration of disease) -No summit lesions - Increased cellulalirity with mild basal accumulation SD, male 40 yrs. old. Levofloxacine 500 mg bid and Metronidazole 500 mg tid started IV fluids/electrolytes, bowel rest Day 3: no improvement , CRP 144 mg/L (60 mg/L on admission) Second stool sample (repeated on day 1): C diff toxine A/B positive CT abdomen: Pancolitis with max. luminal diameter of 6 cm. 6 9/05/2012 What is your diagnosis? • C. difficile colitis • Ischaemia • IBD • IBD and C. difficile 7 9/05/2012 What is your preferred management at this stage? 1. Increase IV metronidazole to 4x 500 mg/d 2. Add oral vancomycine 125 mg 4x/d 3. Start IV steroids 4. Add vancomycine and start IV steroids 5. Refer for colectomy 6. Start cyclosporine 2 mg/kg.d IV 7. Start Infliximab 5 mg/kg IV 8. Other SD, male 40 yrs. old. Oral Vancomycine added Day 6: only partial improvement clinically TPN started Fever down to 37.5 °C Persistent 4 nightly stools, lost 11 kg since onset of symptoms Persistent rectal blood loss and abdominal tenderness No increase in colonic dilatation New sigmoidoscopy: Severe ulcerative colitis, Mayo 3, no upper margin 8 9/05/2012 B-1504566 What is your preferred management at this stage? 1. Add systemic steroids 2. Document clearance of C diff toxine and start systemic steroids 3. Start infliximab 5 mg/kg IV 4. Start cyclosporine 2 mg/kg IV 5. Refer for colectomy 6. Other 9 9/05/2012 SD, male 40 yrs. old. - Started on IV steroids, methylprednisolone 40 mg/d Gradually improving. C diff toxine neg Discharged on Day 5 with oral steroids: Methylprednisolone 32 mg - Readmitted one week later with recurrence of severe colitis Lost 4 more kgs. of body weight C diff toxine neg - Admitted to the hospital Sigmoidoscopy: Mayo 3, severe colitis, no upper margin • Increasing incidence of clostridium difficile-associated diarrhea in inflammatory bowel disease. P. Bossuyt et al. JCC 2009. • Retrospective single referral center cohort on the incidence of CDAD in IBD and non-IBD patients • Electronic hospital database of the laboratory of microbiology • Recruitment period: January 2000 December 2007 – Two periods of equal duration • 01/2000 - 12/2003 • 01/2004 - 12/2007 • Endpoint – Incidence of CDAD • In all patients • In IBD patients – Predisposing risk factors – Outcome IBD versus non-IBD patients 10 9/05/2012 Results: incidence Results: risk factors and outcome • IBD patients significantly younger (p= 0.001) • IBD patients acquired infection more in outpatient setting (p= 0.14) • IBD patients took – less AB in the prior 3 months (p= 0.047) – more immunomodulators (p< 0.001) – Acid suppression no difference • IBD patients had less co-morbidity (p= ns) • No pseudomembranes were seen in IBD patients • Hospital stay in IBD was shorter (p< 0.001) 11 9/05/2012 IBD and C difficile colitis Absence of pseudomembranes in Clostridium difficile-associated diarrhea in patients using immunosuppression agents. – Nomura K e.a. Scan J Gastroenterol 2009; 44: 74-8 • S Benhorin, M Margalit, P Bossuyt et al. The impact of concomitant treatment with immuno-modulators and antibiotics on the outcome of C difficile-associated inflammatory bowel disease exacerbation: an ECCO multi-center retrospective study JCC 2009, 3(1); s62 – 155 pt • 104 AB+IM • 51 AB – Outcome: death or colectomy 3 months • AB+IM 12/104 (12%) • AB 0/51 12